POS1277 LONGTERM IMMUNOGENICITY AND TOLERABILITY OF A 3RD DOSE OF AN mRNA ANTI-SARS-CoV-2 VACCINE IN RA PATIENTS WITH AN INADEQUATE RESPONSE TO A PREVIOUS STANDARD TWO DOSE REGIMEN
Authors: K. Schmiedeberg, I. A. Abela, N. Vuilleumier, S. Pagano, J. Von Kempis, A. Rubbert-Roth
Journal: Annals of the Rheumatic Diseases (2022)

Background Lower seroconversion rates have been reported in patients with rheumatic diseases receiving immunomodulatory therapies following a standard mRNA-based vaccine regimen. Data with regard to immunogenicity and safety of a 3 rd vaccine dose in this patient population is limited 1 . Objectives We aim to study immunogenicity, vaccine associated side effects and the occurrence of flares in RA patients unresponsive to a standard vaccine regimen eligible for a 3 rd vaccine dose. Methods RA patients who had a low or absent anti-S1 response after 12 (Cohort A) or 24 weeks (Cohort B) following a standard vaccination regimen received a 3 rd vaccine dose. Temporary discontinuation of DMARD therapy was recommended. Serum samples were collected before, 2, 12, and 24 weeks after the 3 rd vaccine dose. Quantitative measurement of anti-S was performed using the Roche Elecsys Anti-SARS-CoV-2 spike subunit assay. Neutralizing activity (NT50) against Wuhan WT and αasβ-, γ-, and δ- variants was assessed by using a HIV-based pseudovirus system. Results Baseline characteristics are shown in Table 1. 45/47 patients temporarily discontinued DMARD therapy: Mtx and JAKi were paused one 1 week before/restarted 2 weeks after the 3 rd vaccine dose, bDMARDs were paused 2 weeks before/restarted 2 weeks after the 3 rd dose. Local pain and/or systemic vaccine associated side effects following the 3 rd vaccine dose were reported in 12/17 (71%) in Cohort A, and 10/29 (35%) patients in Cohort B (p = 0.018). Flares were defined as loss of low disease activity (LDA), subsequent to the 3 rd vaccine dose and occurred in 17/47 (36%) patients (p = 0.0332) with comparable frequencies in both cohorts (41% Cohort A, 33% Cohort B (NS)). Table 1. Baseline characteristics of RA patients in Cohort A and Cohort B RA patients (n = 17) Cohort A RA patients (n = 30) Cohort B p-value Age (yrs), mean (± SD) 69 (8) 63.9 (8) NS Female sex, n (%) 9 (53) 13 (43) NS Vaccination type/schedule mRNA-1273/BNT162b2, n= 3/14 5/25 NS RA disease characteristics ACPA ± RF, n (%) 13 (77) 12 (40) 0.02* Disease activity (CDAI ) Remission (≤ 2.8), n (%) 3 (18) 6 (20) NS LDA (2.9 - 10), n (%) 11 (64) 18 (60) NS Moderate CDAI (10.1 - 22.0), n (%) 2 (12) 3 (10) NS High CDAI (22.1 - 76.0), n (%) 1 (6) 3 (10) NS DMARD therapy NS Monotherapy of csDMARDs, n (%) 2/17 (12) 10/30 (33) NS bDMARDs ± csDMARDs, n (%) 8/17 (47) 14/30 (47) NS JAKi ± csDMARDs, n (%) 7/17 (41) 6/30 (20) NS Prednisone, n (%) 5/17 (29) 11/30 (37) NS Mean daily dose prednisone (mg ± SD) 4.1 ± 1.6 4.1 ± 1.5 NS Low or absent anti-S titers were confirmed before the third vaccination (Cohort A: median 19.5 U/ml, IQR 0.47-57; cohort B: median 65.9 U/ml, IQR 22-154) (p = 0.0018). Two weeks after the 3 rd dose, a rapid and significant increase in anti-S were observed in 12/17 (82%) and 25/28 (89%) patients (Cohort A: median 2500 U/ml, IQR 798-2500; Cohort B: median 2500 U/ml, IQR 2500-2500) (NS). High levels of anti-S were maintained in the majority of patients 55% (11/20) until week 12 in both cohorts (Figure 1). NT50 against Wuhan-WT and other variants was assessed in 21 patients 2 weeks after the 3 rd vaccine dose revealing a low or absent NT50 against delta in 38% of patients despite a median anti-S response of 2500 U/ml (IQR 798-2500). 14/21 patients had peak anti-S titres of 2500 U/ml, of those 12/14 developed a strong NT50 response against the delta variant. Figure 1. Conclusion Our data demonstrate that a 3 rd vaccine dose, maybe complimented by temporary discontinuation of DMARD therapy, may lead to a rapid increase in anti-S antibodies when using a homologous vaccine and profound neutralizing activity in the majority of RA patients previously unresponsive to a standard two dose regimen. This seems to be independent of the interval to the previous standard vaccine regimen. As flares occurred in 36% of all patients, the necessity and length of DMARD discontinuation should be explored in more detail to balance between sustained control of disease activity and optimized vaccine induced immune responses. References [1]Schmiedeberg K, et al. Lancet Rheumatol 2022; 4 (1): e11-e13 Disclosure of Interests Kristin Schmiedeberg: None declared, Irene A. Abela: None declared, Nicolas Vuilleumier: None declared, Sabrina Pagano: None declared, Johannes von Kempis Speakers bureau: Lilly, Consultant of: Abbvie, BMS, Pfizer, and Sanofi, Andrea Rubbert-Roth Speakers bureau: Abbvie, Pfizer, Sanofi, UCB, BMS, Lilly, Gilead and Roche, Consultant of: Abbvie, Gilead, Lilly, BMS, and Sanofi